tbuckley/cabot-search huggingface dataset:
Abstract 13114: Micro RNA206 Secreted From Growing Skeletal Muscle Promotes Angiogenic Response in Endothelial Cells
Authors: Hiroya Hayashi, Yasuhiro Izumiya, Toshifumi Ishida, Yuichiro Arima, Ou Hayashi, Kenichi Tsujita, Daiju Fukuda
Journal: Circulation (2022)

Introduction: In addition to aerobic exercise, it has been recognized that resistance exercise has beneficial effects for the patients with peripheral arterial disease. Recently, muscle-derived exosomes are demonstrated to convey many types of signaling molecules including microRNAs (miRNAs). Hypothesis: We assessed the hypothesis that exosomal miRNA secreted by growing muscle promotes angiogenic response in endothelial cells. Methods: We utilized skeletal muscle-specific inducible Akt1 transgenic (Akt1-TG) mice that can induce growth of skeletal muscles without exercise training. Exosomes was purified combined usage of ultracentrifugation, and miRNAs were extracted from purified exosomes by spin column-based method. Real-time PCR array and droplet digital PCR was performed to evaluate exosomal miRNA expression. Results: Akt1-TG mice showed remarkable skeletal muscle growth 2 weeks after gene activation (weight of gastrocnemius muscle: 0.21±0.03 vs 0.16±0.02, g, p&lt;0.01). The amount of exosomal proteins did not different between Akt1-TG mice and WT mice (977.7±11.3 vs 826.0±45.2, μg/mL serum, p=0.07). KEGG pathway frequency analysis for 4665 target genes identified by real-time PCR array of miRNAs revealed a significant increase in Akt and its downstream signaling pathways. Among upregulated miRNAs, droplet digital PCR identified that miR-1, -133 and -206 expression was significantly upregulated in Akt1 TG mice compared with WT mice in serum. miR206 was increased in IGF-1-stimulated myotubes. PKH26-labeled exosomes were taken up by human umbilical vein endothelial cells. Exogenous supplementation of exosomal miRNA206 promoted angiogenesis as revealed by spheroid assay, and increased expression of HIF-1 and VEGF in endometrial cells. Conclusions: Exosomal miR206 was upregulated in blood stream in Akt1-TG mice and IGF-stimulated cultured myotubes. Exogenous supplementation of miR206 promoted angiogenic response in endothelial cells. Our data suggest that miR206 secreted from growing muscle act on endothelial cells and promote angiogenesis.
Abstract 13807: Sex Differences in Patients Characteristics, Risk Factors, and Symptomatology in Older Adults With Pulmonary Embolism: Findings From the SERIOUS-PE Study
Authors: Behnood Bikdeli, David Jimenez, Gregory Piazza, Alfonso Muriel, yun wang, Candrika D Khairani, Rachel Rosovsky, Olga Madridano, Juan Bosco Lopez-Saez, Meritxell Mellado, Ana María Diaz Brasero, Ghazaleh Mehdipoor, Michelle O'Donoghue, Primavera A Spagnolo, Yuan Lu, Laurent BERTOLETTI, Luciano Lopez-Jimenez, Manuel J Nunez-Fernandez, Angeles Blanco-Molina, Shannon Bates, Marie Gerhard-Herman, Samuel Goldhaber, Manuel Monreal, Harlan M Krumholz
Journal: Circulation (2022)

Background: Biological sex is linked with pulmonary embolism (PE) disease presentation in young patients, such as the risk incurred by pregnancy. Whether sex differences exist in PE presentation, co-morbidities, risk factors, and symptomatology in older adults, the age group in which most of these events occur, remains unknown. Methods: We identified older adults (aged ≥65 years) with PE in a large international PE registry that is replete with granular clinical information about clinical characteristics and PE symptoms (RIETE registry, 2001-2021). To provide national data from the USA, we assessed sex differences in risk factors and clinical characteristics of US Medicare beneficiaries with PE (2001-2019). Results: The majority of older adults with PE in RIETE (19,294/ 33,462, 57.7%) and in Medicare database (551,492/ 948,823, 58.7%) were women (Panel A). Compared with men, women with PE less frequently had atherosclerotic diseases, obstructive lung disease, cancer, or unprovoked PE, but more frequently had a varicose veins, depression, prolonged immobility, or history of hormonal therapy (P&lt;0.001 for all, Panel B). Compared with men, women less often presented with chest pain (37.3% vs 40.6%) or with hemoptysis (2.4% vs 5.6%), but more often presented with dyspnea (84.6% vs 80.9%) (P&lt;0.001 for all). The proportions of patients with syncope (16.4% vs 15.9%) and patients with simplified Pulmonary Embolism Severity Index &gt;0 (76.3% vs 75.0%) were comparable. Conclusions: In routine practice, elderly women constitute the largest proportion of patients with PE. Sex differences exist in risk factors and clinical presentation of older adults with PE, with cancer and cardiovascular disease being more common in men; and transient provoking factors such as immobility or hormone therapy being more common in women. Whether such differences correlate with disparities in treatment, or differences in short- or long-term clinical outcomes warrant further investigation.
Abstract 12891: Protocol Driven Therapeutic Efficacy of Intravenous Unfractionated Heparin in the Current Era
Authors: Kayla Torppey, manpreet kaur, Natale Wasef, Sandra Richardson, Marc Cohen
Journal: Circulation (2022)

Introduction: Despite years of refining algorithms, intravenous (IV) unfractionated heparin (UFH) is associated with many limitations in the inpatient setting. Low-molecular-weight heparin (LMWH) has shown to be equivalent to UFH in the treatment of acute venous thromboembolic disease (VTE), and demonstrated superiority in acute coronary syndrome (ACS). LMWH has less pharmacokinetic variability, a longer plasma half-life, and is associated with fewer complications. UFH also requires frequent activated partial thromboplastin time (aPTT) monitoring, affecting hospital resources. The objectives of this study were to assess the real-word therapeutic impact of routine IV UFH use in the setting of a hospital-based algorithm, evaluate the number of patients eligible for substitution with LMWH, and estimate the cost differential. Hypothesis: Methods: Adult patients who received greater than 24 hours of IV UFH from 8/1/21 to 9/30/21 (n=174), were included in this retrospective evaluation. A random sample of 100 of these 174 patients was analyzed for aPTT results in hours 25-48. These 100 patients were also considered for theoretical substitution with LMWH. Ineligibility for substitution included intermittent and continuous renal replacement therapy (RRT), creatinine clearance less than 30 mL/min, and a planned invasive procedure within 24 hours. Fiscal analyses were also done. Results: Among 519 aPTTs drawn from these 100 patients, 348 (67%) were not within the hospital therapeutic range. The most common indications for anticoagulation were ACS and acute VTE. Eighty-one percent of patients on UFH were eligible for LMWH substitution. Ineligibility was most commonly secondary to renal dysfunction. Estimated drug acquisition costs were similar, but overall cost was lower with LMWH due to decreased laboratory testing, nurse/patient contact time, and infusion supplies. Conclusions: In spite of current hospital-based algorithms and electronic order sets to minimize variability, achieving a therapeutic aPTT during the day after UFH initiation, remained elusive. The majority of patients receiving IV UFH were eligible for substitution with LMWH. Patients who qualify, should be placed on the simpler and more reliable antithrombotic LMWH regimen.
Abstract 13915: Man vs. Machine: A Direct Comparison of the Diagnostic Efficacy of Novel Automated WCT Differentiation to Traditional Manual ECG Interpretation Approaches
Authors: Sarah LoCoco, Anthony H Kashou, Abhishek Deshmukh, Samuel Asirvatham, Peter A Noseworthy, Christopher V Desimone, Daniel Cooper, Phillip S Cuculich, Sandeep Sodhi, Adam May
Journal: Circulation (2022)

BACKGROUND: Differentiation of wide QRS complex tachycardias (WCTs) into ventricular tachycardia (VT) and supraventricular wide QRS tachycardia (SWCT) through 12-lead electrocardiogram (ECG) interpretation is one of the most critical yet challenging tasks in clinical practice. Recent research highlights novel automated methods that successfully diagnose WCTs. We sought to directly compare the diagnostic efficacy of these novel automated WCT differentiation methods (i.e., WCT Formula, VT Prediction Model, and WCT Formula II) to traditional ECG interpretation approaches (i.e., Brugada and Vereckei aVR algorithms). METHODS: A collection of paired WCT and baselined ECGs were retrospectively analyzed. Next, an electrophysiologist blindly and prospectively applied the Brugada and Vereckei aVR algorithms. Separately, computerized measurements were used to apply the three automated WCT differentiation methods. The diagnostic performance of each method was then evaluated. RESULTS: 213 WCTs (111 VT and 102 SWCT) from 105 patients were analyzed. The WCT Formula demonstrated superior overall accuracy (84.7% vs. 64.8%), specificity (86.2% vs. 35.3%), positive predictive value (PPV) (85.7% vs. 60.7%), and positive (+) likelihood ratio (LR) (6.06 vs. 1.42) compared to Vereckei aVR algorithm. Similarly, the WCT Formula attained higher specificity (86.2% vs. 61.8%), PPV (85.7% vs. 71.9%), and (+) LR (6.06 vs. 2.36) than the Brugada algorithm. The WCT Formula II demonstrated superior overall accuracy (89.2% vs. 64.8%), specificity (84.3 % vs. 35.3%), PPV (86.7% vs. 60.7%), and positive (+) LR (5.97 vs.1.42) compared to Vereckei aVR algorithm as well as higher specificity (84.3 % vs. 61.8 %), PPV (86.7% vs. 71.9%), and (+) LR (5.97 vs. 2.36) than the Brugada algorithm. The VT prediction model yielded superior specificity (79.4% vs. 35.3%), PPV (79.8 vs. 60.7%) and (+) LR (3.63 vs.1.42) compared to the Vereckei aVR algorithm but did not demonstrate superior diagnostic performance to the Brugada algorithm. CONCLUSIONS: Novel automated WCT differentiation methods achieved similar or superior diagnostic performance metrics compared to traditional ECG interpretation approaches.
Abstract 13215: Accuracy of Visual Qualitative Estimates of CAC Incidentally Found on Chest CT Compared With Formal CAC Scoring
Authors: Viraj Raygor, Parag H Joshi, Arzu Canan, Suhny Abbara, Joanna N Assadourian, Amit Khera, Eric D Peterson, Ann M Navar
Journal: Circulation (2022)

Introduction: While coronary artery calcium (CAC) scoring improves CVD risk assessment, it remains underutilized and is often not covered by insurance. Coronary calcium can be detected on chest CT scans performed for other indications and may allow identification of higher-risk people without a dedicated CAC scan. However, qualitative CAC scoring on non-gated chest CT scans is not widely validated. Methods: Since 2016, radiologists at two large health systems in Dallas (an academic medical system and a large safety net hospital) have routinely documented the presence and severity of CAC (none, mild, moderate, large) on all chest CT scans. We identified all adults who underwent both dedicated CAC scanning and a separate chest CT scan within 6 months. We compared qualitative visual CAC by CT scan versus a CAC score from a dedicated, gated coronary CT scan. Results: From 2016-2021, 891 patients (mean age 60 ± 12y, 43% male, 61% White, 35% Black, 24% Hispanic) underwent both a CT scan and a CAC score. Of these, 424 had no CAC, 268 small, 137 moderate, and 62 large CAC on CT scan. Qualitative CAC estimate from non-gated CT scans were highly correlated with formal CAC scores (Kendalls tau-b=0.75, p&lt;0.0001, figure). To detect CAC (score &gt;0), qualitative assessment on CT had a sensitivity of 82%, specificity of 95%, positive predictive value (PPV) of 97%, and negative predictive value (NPV) of 77%. Only 6% with small, 1% with moderate, and 0% with large CAC on CT had a CAC score = 0. For detection of CAC ≥ 100, moderate to large CAC on CT had a sensitivity of 62%, specificity of 96%, PPV of 89%, and NPV of 84%. Discussion: At two different hospitals serving a diverse population, visual estimates of CAC on routine CT scans were strongly correlated with formal CAC scores from dedicated, gated CT scans. Incidental identification of CAC on routine CT scans should prompt more aggressive cardiovascular risk reduction, particularly when moderate to large CAC burden is seen.
Abstract 14793: The Mediating Effect of Resilience on the Relationship Between Self-Care Activation, Hope, and Medication Adherence in a Diverse Sample of Adults With Heart Failure
Authors: Rebecca Meraz, Jocelyn McGee, Elizabeth Perry, Weiming Ke, Kathryn A Osteen
Journal: Circulation (2022)

Background: Despite decades of research and advances in treatment, medication adherence in those with heart failure remains suboptimal. Recent research suggests that self-care activation and positive psychological characteristics can enhance medication adherence, yet little is known about how these factors and medication adherence are related in persons with heart failure. Objective: The purpose of this study was to investigate whether the effects of self-care activation and hope on medication adherence are mediated by resilience in persons with heart failure. Methods: This study used a prospective, cross-sectional design. Regression and mediation analyses were used to examine if resilience mediates the effects of activation on medication adherence. A nationwide, diverse sample was recruited for this study. Results: Of the 174 participants, 51% were female, 48% were persons of color (POC) and the mean age was 62 years. Higher activation (B = -.023, p = .039) and hope (B = -.063, p = .011) were associated with better medication adherence. The effects of activation and hope on medication adherence were completely mediated by resilience. Indirect effect accounts for 17.4% of the total effect for activation and 71.4% for hope. Conclusion: Resilience could be a potential mechanism by which activation and hope could improve medication adherence in persons with heart failure. Thus, resilience may have a significant influence on medication adherence. More research is needed to understand the connection between resilience and medication adherence.
Abstract 13382: Outcomes of Patients With Valvular Cardiogenic Shock Stratified by Treatment Strategy
Authors: Raunak M Nair, Feras Alkhalaileh, Sanchit Chawla, Bahaa Abdelghaffar, Umesh N Khot, Andrew Higgins, Ran Lee, Wael A Jaber, Paul C Cremer, Penelope Rampersad, Venu Menon
Journal: Circulation (2022)

Background: No prior studies have compared the outcomes of patients with valvular cardiogenic shock (VCS) depending on the treatment received. Our study aimed to assess this. Methods: All patients admitted to Cleveland Clinic Cardiac Intensive Care Unit (CICU) between Jan 1 st , 2010, to Dec 31 st , 2021, with a diagnosis of cardiogenic shock (CS) were retrospectively identified through electronic medical records and confirmed via physician directed chart review. Patients with CS were subsequently categorized into those with valvular cardiogenic shock (VCS) and non-valvular CS depending on the primary etiology responsible for hemodynamic instability. The impact of treatment strategy on 1-year all-cause mortality in patients with VCS was assessed with Kaplan-Meier (KM) estimates. Results: Overall 511 patients were admitted to our CICU with VCS during the study period. Out of these patients, 188 patients (37%) underwent surgery, 76 patients (15%) underwent percutaneous structural intervention, and 247 patients (48) % underwent conservative management. Comparison of baseline characteristics (Table 1) revealed that patients with VCS who underwent surgical treatment were significantly younger (median age 64 yrs vs 72 and 76 yrs, p&lt;0.001), and less likely to have coexisting comorbidities such as diabetes, dyslipidemia, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). KM survival analysis revealed that VCS patients who underwent conservative management had the highest all-cause mortality at 1 year, whereas those patients who underwent surgery had the lowest all-cause mortality at 1 year (p&lt;0.001) (Figure 1). Conclusion: Patients with VCS remain a high-risk cohort who are most likely to be conservatively managed. Of the patients who received a specific therapy, surgical management was associated with the best outcomes. The impact of early intervention in patients with VCS needs to be further explored.
Abstract 13441: Transcriptomic Analysis of Endothelial Colony Forming Cells From the BioHEART-CT Study to Unravel New Biomarkers for Coronary Artery Disease
Authors: Hooi H Ng, Marie Besnier, Kirsten Schnitzler, Andy Tran, Jean Y Yang, Gemma A Figtree
Journal: Circulation (2022)

Coronary artery disease (CAD) remains the leading cause of death worldwide. There are unmet needs for the diagnosis and treatment for patients with CAD, especially those without modifiable risk factors who are suspected to be at low risk for CAD. Endothelial function has predictive value for future cardiovascular events. We previously showed that endothelial colony forming cells (ECFCs) derived from the BioHEART-CT (The BioHEART Study: Assessing Patients with Suspected Cardiovascular Disease for New Biomarkers and Risk Factors) cohort can be used as a viable tool to evaluate endothelial function in patients as these cells retain the memory of their host. Here, we aimed to characterize the transcriptomic profiles of ECFCs in non-CAD and CAD patients. Based upon our previous findings on the positive correlation between mitochondrial superoxide level and the severity of CAD, we hypothesize that the transcriptomic and functional analyses of the mitochondrial pathways are dysregulated in the ECFCs in CAD patients. RNA-sequencing was performed in ECFCs cultured from the peripheral blood of 44 patients from the BioHEART-CT cohort who had computed tomography coronary angiograms scored for coronary artery calcium (CAC) and Gensini to measure CAD severity. The cohort included 45.5% women and 54.5% men with an average age of 61.6 years. Non-CAD group was determined by a Gensini score of zero, whereas CAD group was determined by a Gensini score of greater than 5. These CAD patients had median CAC score of 266.8, with significant presence of calcified and soft plaques in their coronary arteries. Transcriptomic analysis of ECFCs showed that a total of 37 genes were upregulated and 77 genes were downregulated in the CAD patients. To investigate the functional relevance of the pathways altered in the CAD cohort, dysregulation of genes was analyzed using gene set enrichment analysis. We found that the metabolic processes, those associated with mitochondrial biogenesis, were significantly altered in the ECFCs. Our approach of using RNA-sequencing to determine the gene characteristics of CAD patients and their functional relevance to disease has the potential to unravel previously un-identified genes or biomarkers that are distinct to CAD patients.
Abstract 14012: Association Between Direct Oral Anticoagulant Concentration Upon Acute Stroke and Stroke Outcomes
Authors: Shin Yi Lin, Sung-Chun Tang, Ching-Hua Kuo, Chih-Fen Huang, Jiann S Jeng
Journal: Circulation (2022)

Introduction: Ischemic stroke (IS) or intracranial hemorrhage (ICH) has been reported during direct oral anticoagulant (DOAC) therapy. However, data regarding the DOAC level upon acute stroke is lacking. Hypothesis: The DOAC level upon acute IS or ICH may be associated with stroke outcomes. Methods: Patients aged ≥ 20 years, under DOAC therapy and developed acute ischemic or hemorrhagic stroke were enrolled. The DOAC level upon hospital arrival was measured with ultra-high-performance liquid chromatography with tandem mass spectrometry. The primary outcome was the composite outcomes included IS, ICH, major bleeding or death at 3 months. The secondary outcome included modified Rankin Scale (mRS) 0 to 3 at 3 months. Results: During 2018 to 2022, a total of 105 patients who developed IS and 26 patients who developed ICH during DOAC therapy were enrolled. Among the IS cohort, 45 (42.9%) had DOAC level&lt;50 ng/mL. The initial National Institutes of Health Stroke Scale (NIHSS) was similar between patients with DOAC level &lt;or≥50 ng/mL. The primary outcome occurred in 13 and 9 patients with DOAC level&lt;or≥ 50 ng/mL. After adjustment, factors associated with composite outcomes at 3 months included reduced creatinine clearance (HR=0.96 [0.93, 0.995]), higher initial NIHSS (HR=1.08 [1.01, 1.15]) and DOAC level&lt;50 ng/mL (HR=5.63 [1.47, 21.65]). To predict mRS 0 to 3 at 3 months, initial NIHSS, and DOAC level&lt;50 ng/mL displayed inverse association (OR=0.82 [0.75, 0.90] and 0.19 [0.05, 0.78]). Among the ICH cohort, 19 patients (73.1%) has DOAC level&lt;50 ng/mL. Compared to patients with DOAC level≥50 ng/mL, their initial hematoma size was smaller. The primary outcome occurred in 0 and 5 patients with DOAC level &lt;or≥ 50 ng/mL. The proportion of patients with hematoma expansion and having mRS 0 to 3 points were similar between patients with DOAC level&lt;or≥50 ng/mL (40.0% versus 43.8%, p=1.00 for hematoma expansion; 85.7% versus 52.6%, p=0.19 for mRS 0 to 3 points). Conclusion: Among patients who develop IS during DOAC therapy, low DOAC level, along with higher initial NIHSS and worse renal function, predicts worse clinical outcomes.
Abstract 14365: In-Hospital Outcomes of Septal Myectomy versus Alcohol Septal Ablation for Hypertrophic Cardiomyopathy - An Update and Insights From the National Inpatient Sample
Authors: Karla Inestroza, Ian Ergui, Carlos Matute-Martinez, michael Albosta, Carlos Vergara-Sanchez, Michael Dangl, Rafael J Hernandez, Bertrand Ebner, Louis T Vincent, Jelani Grant, Jennifer Maning, Carlos Alfonso, Rosario Colombo
Journal: Circulation (2022)

Introduction: Septal Myectomy (SM) and Alcohol Septal Ablation (ASA) improve symptoms in patients with Hypertrophic Cardiomyopathy (HCM), however, outcomes data in this population is predominantly from specialized centers. Methods: The National Inpatient Database was queried from 2011- 2019 for relevant ICD-9 and -10 diagnostic and procedural codes. Baseline characteristics and in-hospital outcomes of patients with HCM who underwent SM vs. ASA were compared. A p-value &lt;0.001 was considered statistically significant. Results: We identified 17,245 patients who underwent septal reduction therapies, of whom 62.5% underwent SM and 37.5% underwent ASA. Patients who underwent SM had higher all-cause mortality (OR:2.2 [1.7-2.9]), post procedure ischemic stroke (OR: 2.4 [1.8-3.2]), acute kidney injury (OR: 1.9 [1.7-2.2]), vascular complications (OR: 4 [2.8-5.7]), ventricular septal defect (OR: 4.6 [3.5-6.1]), aortic dissection/aneurysm (OR: 1.6 [1.3-2.1]), cardiogenic shock (OR: 2 [1.5-2.6]), sepsis (OR:5.2 [3.3-8.1]), and left bundle branch block (OR: 3.2 [2.8-3.7]) (p&lt;0.001 for all), compared to ASA. Patients who underwent ASA had higher post procedure complete heart block (OR: 1.2 [1.1-1.4]), 2 nd -degree AV Block (OR: 2 [1.4-3]), right bundle branch block (OR: 6.4 [5.3-7.8]), ventricular tachycardia (OR:2 [1.8-2.3]), supraventricular tachycardia (OR: 1.4 [1.2-1.7]), and more commonly required pacemaker (OR: 1.4 [1.2-1.6]) or implantable cardioverter-defibrillator (OR: 1.3 [1.1-1.5]) (p&lt;0.001 for all) insertion compared to SM. Conclusions: This nationwide analysis evidenced patients undergoing SM had higher in-hospital mortality and periprocedural complications compared to ASA, however, those undergoing ASA had higher post-procedure conduction abnormalities and pacemaker or ICD implantation. The implications of these findings warrant further investigation in regards to patient selection strategies for these therapies.